We used IMV, corticosteroids, and antiviral drugs for severe or critically ill COVID-19 patients at the beginning of 2020. However, these therapies caused many adverse events and a prolonged ICU stay. Therefore, we decided to switch to the therapeutic combination of early PP and HFNC to treat patients with COVID-19.
The PP has some benefits in ARDS [15], and the WHO recommends the use of the PP in patients with severe COVID-19 [3]. It was reported that a prolonged PP (over 12 hours) improved the outcome of patients with ARDS [16]. We set the length of the PP based on its effectiveness. Some studies concluded that the PP improves short-term oxygenation [15, 17], and PP was effective in avoiding tracheal intubation [8, 18]. However, another published study reported that this effect was not maintained after resupination for a short time [19]. We noted that the SpO2 of all patients including patients requiring NIV or IMV later improved immediately on placing them in the PP. Although all patients requiring NIV or IMV maintained PP over 6 hours, which is our criteria as the effective PP, they finally required NIV or IMV. Given that results, we concluded that the cutoff wasn’t suitable and patients had to maintain the PP longer to avoid NIV or IMV use.
Almost all patients said “I could not maintain a prolonged PP owing to my tiredness and myalgia”. We used several methods to facilitate a prolonged PP: first, we placed vital signs monitors where patients were able to view the changes in their SpO2 themselves, and felt motivated to maintain a prolonged PP; second, we permitted the use of electronic devices for the patients (Fig. 1). We believed that putting a lot of thought into maintaining a prolonged PP was one of the most important factors in the success of COVID-19 treatment.
However, the disadvantage of PP is the inherent difficulty in changing the patient’s position. Placing intubated patients in the PP requires the help of several staff members, and caution should be exercised so that the intubation circuit is not disturbed; thus, patients cannot move to the PP on their own. This prevented frequent repositioning. From this point of view, HFNC may be useful in solving this problem. Patients with HFNC are usually awake and can switch to the PP on their own; furthermore, HFNC can be easily reattached on the face of a patient. For these reasons, we believe that the combined therapeutic use of HFNC and PP is a good strategy for treating critical COVID-19 patients. Other benefits of treatment with an HFNC are that it is well tolerated, can wash out of the nasopharyngeal dead space, reduce the work related to gas conditioning, improve mucociliary clearance, generate low levels of positive end-expiratory pressure, and protect the lungs from self-induced lung injury [20, 21]. A few studies on the use of HFNC in COVID-19 patients have been published [22, 23, 24]. The first study reported that HFNC is a good treatment option for patients with COVID-19; however, others reported the opposite. The third study reported that HFNC failure occurred in 63% of patients when the P/F ratio was below 200. The authors concluded that the success rate of HFNC seems to be mostly dependent on the severity of pulmonary infection.
In a multicenter, adjusted cohort study that evaluated whether combination therapy with HFNC and PP improved the outcomes of COVID-19 patients than in those treated with PP alone, the risk of intubation was not decreased in patients who underwent combination therapy with HFNC and PP. Furthermore, the authors suggest that an awake PP could have a potentially negative impact as it was associated with a delay in intubation [4]. In this study, the intubation rate was 40%. In comparison, few patients required IMV in our study (6% vs. 40%). We believe that the previous study did not have good HFNC-related outcomes as patients with an SpO2 < 93% with a non-rebreather face mask at 15 L/min were included in the study; at this point, it is generally too late to initiate treatment with HFNC. Another case series has reported that no patient with early HFNC initiation and prolonged PP were intubated [8]. These authors suggested that an early awake PP combined with HFNC therapy was one of the most important strategies to avoid tracheal intubation and reduce the requirement for medical staff. We also consider this treatment to be the most effective and feasible strategy for severe or critical COVID-19 patients. Medical providers caring for patients with COVID-19 have noted that therapy with early HFNC combined with PP improves respiratory function markedly in critical patients in real-life clinical situations.
There have been some studies on mortality in COVID-19 patients who use HFNC. In the ACTT-1 study, the mortality rate at day 29 in patients with HFNC or NIV was 20% [25]; although it is not known how many patients were treated with HFNC combined with PP in this study, that result is inferior to our result (20% vs. 11%). Moreover, if we exclude patients who are not eligible for IMV due to their PS, the presence of comorbidities, or the wishes of the patient or their family, only two patients (4%) who underwent HFNC died in our study. We consider that the use of not only HFNC but also the PP makes the difference in the mortality rate. Another study reported that the 28-day mortality rate in patients with the combination of HFNC and PP was 12%, which was similar to that in our study (11% vs. 12%) [24].
When we decided to introduce HFNC as a treatment modality for critically ill patients with COVID-19, its potential safety, that is, whether using HFNC generated aerosols and spread the virus, was questioned. HFNC has been reported to have a low risk of bio-aerosol dispersion [26]. Furthermore, it was also reported that using surgical masks among COVID-19 patients could prevent person-to-person transmission [27]. Based on this report, patients with HFNC were instructed to use a surgical mask over an oxygen delivery device. Only one staff member working in the ICU was infected with SARS-CoV-2 during the study period. It was unclear whether the infection was transmitted to this staff member by the COVID-19 patients in the ICU.
This study has several limitations. First, this study was performed in a single center. Second, we did not strictly define the criteria for HFNC initiation. The decision of HFNC initiation was discussed on a daily basis by specialists. We considered that the SpO2 threshold for HFNC initiation was SpO2 < 90% with a non-rebreather mask at 7 L/min, which is earlier than the threshold in other studies. Third, the duration of the PP was not recorded accurately. Because patients were awake and felt mild dyspnea, they sometimes turned to the supine position by themselves, which made it difficult to record the exact PP duration. Most importantly, we did not consider the other therapies received by the patients in this study. Almost all patients in this study received other therapeutic agents, including remdesivir, corticosteroids, tocilizumab, and heparin calcium, which are considered as important agents for COVID-19 treatment. In particular, all patients were administered MPP, and nine patients were administered tocilizumab to effectively suppress inflammation. The RECOVERY trial revealed the efficacy of dexamethasone [28], and another study reported the efficacy of MPP [29] in patients with COVID-19. Thus, concomitant therapy may have affected our results.